Table 1.
A summary of clinical trials of immune checkpoint inhibitors (anti-PD-1, CTLA4, and TIM-3 antibodies) for AML and/or MDS. HL: Hodgkin lymphoma, NHL: non-Hodgkin lymphoma, MM: multiple myeloma, MPN: myeloproliferative neoplasm, ALL: acute lymphoid leukemia, CML: chronic myeloid leukemia, CLL: chronic lymphocytic leukemia, RCC: renal cell carcinoma, allo-HSCT: allogeneic hematopoietic stem cell transplantation, HMA: hypomethylating agent, CR: complete remission, CRi: CR with incomplete hematologic recovery, HI: hematologic improvement, PR: partial remission, SD: stable disease, OS; overall survival.
| Author | Object(s) | Disease State | Agent(s) | Dosing | Phase | Response Rate | Median Survival | |
|---|---|---|---|---|---|---|---|---|
| Daver, et al., 2016 |
AML | Relapsed after prior therapy | Nivolumab | 3 mg/kg on Day 1, 14 (every 4–5 weeks) | Ib/II | CR/CRi HI |
18% (6/51) 15% (5/51) |
9.3 mo. [1.8–14.3] |
| + Azacitidine | 75 mg/m2 on Day 1–7 (every 4–5 weeks) | |||||||
| Daver, et al., 2018 |
AML | Relapsed or refractory | Nivolumab + Azacitidin |
[Cohort 1] Not Reported | II | CR/CRi HI Prolonged SD |
21% (15/70) 10% (7/70) 9% (6/70) |
16.1 mo. |
| Nivolumab+ Azacitidin+ Ipilimimab | [Cohort 2] Not Reported | II | CR/CRi Prolonged SD |
36% (6/20) 10% (2/20) |
Not Reached (1-yr. OS 58%) | |||
| Ravandi, et al., 2019 |
AML and high-risk MDS | Newly diagnosed | Idarubicin + Cytarabine + Nivolumab |
12 mg/m2 on Day 1–3 1.5 g/m2 on Day 1–4 3 mg/kg (every 2 weeks) *started on Day 24 |
II | CR/CRi Negative MRD |
78% (34/44) 41% (18/34) |
18.5 mo. [10.8–28.8] |
| Davids, et al., 2016 |
Hematologic malignancies (AML, HL, NHL, MDS, MM, MPN, ALL) |
Relapsed after allo-HSCT | Ipilimumab | 3 or 10 mg/kg (every 3 weeks for 4 doses then every 12 weeks for upto 6 doses) *All reseposive cases recieved 10 mg/kg. |
I/Ib | CR PR |
23% (5/28) 9% (2/22) |
Not Reported |
| Bashey, et al., 2009 |
Malignancies (AML, HL, NHL, MM, CML, CLL, Breast cancer, RCC) |
Relapsed after allo-HSCT | Ipilimumab | 0.1 to 3.0 mg/kg (every 60 days) *Dose-escalating model. |
I | CR PR |
6.9% (2/29) 3.4% (1/29) |
24.7 mo. |
| Zeidan, et al., 2018 |
MDS | Refractory to HMAs | Ipilimumab | 3 or 10 mg/kg (every 3 weeks for 4 doses then every 12 weeks for upto 8 doses) |
I | Marrow CR Prolonged SD |
3.4% (1/29) 24% (7/29) |
Not Reported |
| Lindblad, et al., 2018 |
AML | Relapsed or refractory | Pembrolizumab + Decitabine |
200 mg/body (every 3 weeks) 20 mg/m2 on Day 8–12, 15–19 (every 6 weeks) |
I/II | CR SD |
10% (1/10) 40% (4/10) |
7 mo. [2,3,4,5,6,7,8,9,10,11,12,13,14] |
| Borate, et al., 2019 |
AML and high-risk MDS | Ineligible to standard therapy | MBG453 (anti-TIM-3) + Decitabine |
Escalating dose from 240 to 800 mg/body (every 2 weeks or 4 weeks) 20 mg/m2 on Day 1–5 (every 4 weeks) |
Ib | CR/CRi PR Blasts halved |
23% (7/31) 6% (2/31)2 6% (8/31) |
Exposure durations 2.1–17.9 months |